MDL 201053 Chemical Properties

Boiling point:

630.5±55.0 °C(Predicted)

Density 

1?+-.0.06 g/cm3(Predicted)

solubility 

DMSO: soluble

pka

11.07±0.46(Predicted)

MDL 201053 Usage And Synthesis

Description

Z-FA-FMK is an inhibitor of cathepsin B (Ki = 1.5 µM).1 It also is an inhibitor of caspase-2, -3, -6, -7, and -9 (IC50 = 6.147, 15.41, 32.45, 9.077, and 110.7 µM, respectively).2 Z-FA-FMK inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), also known as 3C-like protease (3CLpro), in a cell-free assay (IC50 = 11.39 µM).3 It inhibits SARS-CoV-2 replication in infected Vero E6 cells (EC50 = 0.13 µM) without inducing cytotoxicity in the same cells with a 50% cytotoxic concentration (CC50) value of >20 µM. Z-FA-FMK (50 µM) decreases the proliferation of, and levels of glutathione (GSH) in, and increases levels of reactive oxygen species (ROS) in anti-CD3-stimulated primary human peripheral blood mononuclear cells (PBMCs).4 It inhibits LPS-induced increases in levels of IL-1β in PU5-1.8 macrophages and Nf-κB transactivation in Mf4/4 macrophages when used at a concentration of 50 µM.5WARNING This product is not for human or veterinary use.

References

[1] ROGER A. SMITH. Inhibition of cathepsin B by peptidyl aldehydes and ketones: slow-binding behavior of a trifluoromethyl ketone[J]. Biochemistry Biochemistry, 1988, 27 17: 6568-6573. DOI: 10.1021/bi00417a056
[2] FRANCISCO J LOPEZ-HERNANDEZ. Z-FA-fmk inhibits effector caspases but not initiator caspases 8 and 10, and demonstrates that novel anticancer retinoid-related molecules induce apoptosis via the intrinsic pathway.[J]. Molecular Cancer Therapeutics, 2003, 2 3: 255-263.
[3] WEI ZHU, WEI ZHENG*   Identification of SARS-CoV-2 3CL Protease Inhibitors by a Quantitative High-Throughput Screening[J]. ACS Pharmacology and Translational Science, 2020, 3 5: 1008-1016. DOI: 10.1021/acsptsci.0c00108
[4] TANUJA RAJAH  Sek C C. Suppression of Human T Cell Proliferation Mediated by the Cathepsin B Inhibitor, z-FA-FMK Is Due to Oxidative Stress.[J]. PLoS ONE, 2015: e0123711. DOI: 10.1371/journal.pone.0123711
[5] P. SCHOTTE. The Cathepsin B Inhibitor z-FA.fmk Inhibits Cytokine Production in Macrophages Stimulated by Lipopolysaccharide*[J]. The Journal of Biological Chemistry, 2001, 1 1: 21153-21157. DOI: 10.1074/jbc.m102239200